Project Summary/Abstract This application is in response to the NIA?s Strategic Directions Goal D-3, which calls for better tools to assess cognitive function in the clinic, primary care setting, and home environment in order to distinguish persons at risk for developing Alzheimer?s disease (AD) from persons not at risk. Persons living with HIV (PLHIV) are now living well into the age demographic in which they are at increasing risk for developing AD. Because up to 50% of PLHIV experience cognitive impairment from HIV or related factors that often include memory problems, AD may go unidentified in a significant proportion of older PLHIV. There is a pressing need in geriatric neuroHIV for the ability to accurately identify and disentangle HIV- and AD-associated cognitive impairment and predict individuals who are at risk for further cognitive decline. Evidence from epidemiological studies suggests that sensory (e.g., auditory processing) and motor (e.g., balance) impairments are observed more frequently in PLHIV compared to the general population of a similar age and that these impairment may impact the progression of cognitive impairment in PLHIV and in AD. Building on substantial evidence demonstrating that virtual reality is widely accepted among older adults, we propose to use a novel and portable 3-D virtual reality automated tool, called DETECT, to accurately measure cognition decline and changes in postural stability over time in older PLHIV with and without amnestic mild cognitive impairment (aMCI), a precursor to AD. DETECT was developed for rapid and brief cognitive testing in diverse settings, such as busy geriatric HIV clinics or the home, and can accurately discriminate between normal cognition, MCI, and dementia. Additionally, our pilot work indicates that DETECT is a sensitive screening tool for differentiating between normal cognition and HIV-associated neurocognitive disorder (HAND) in PLHIV. The system is also accurate for diagnosing postural instability using a novel technique that obviates the need for standing and ambulation. To expand on this work, we propose a two site (UCSD and Emory) prospective study of 120 older individuals representing three different clinical phenotypes: PLHIV with HAND and aMCI (HAND+/aMCI+), PLHIV with HAND but without aMCI (HAND+/aMCI-), and HIV-uninfected persons with aMCI (HIV-/aMCI+). An empirically-based neuropsychological diagnostic approach will be used to identify aMCI among PLHIV. We will use DETECT to: (Aim 1) compare the determinants of cognitive decline in these groups, and (Aims 2 and 3) understand how non-cognitive functional changes such as postural instability, hearing loss, and central auditory processing dynamically influence cognitive decline in these groups. Our longitudinal study design will allow us to better understand how cognitive change differs over time between these groups of individuals. The long-term goal of this work is to bring rapid, accurate tools that can identify those at increased risk for progression to AD dementia into clinical practice. The eventual adoption of such tools into clinical practice could provide clarity to patients and clinicians, alleviate fears among PLHIV who do not have aMCI, improve efficiency, and guide the triage of individual patients into specific treatment pathways.